Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study
ABSTRACT Introduction The cystatin family is particularly relevant in lung cancer research due to its links to inflammation, protease balance, and tumor progression. Although population‐based studies have documented associations between cystatin and lung cancer, causal relationships remain undetermi...
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Wiley
2025-07-01
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| Series: | The Clinical Respiratory Journal |
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| Online Access: | https://doi.org/10.1111/crj.70112 |
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| author | Chunling Zhang Riya Wu Hang Liu Shihuan Yu |
| author_facet | Chunling Zhang Riya Wu Hang Liu Shihuan Yu |
| author_sort | Chunling Zhang |
| collection | DOAJ |
| description | ABSTRACT Introduction The cystatin family is particularly relevant in lung cancer research due to its links to inflammation, protease balance, and tumor progression. Although population‐based studies have documented associations between cystatin and lung cancer, causal relationships remain undetermined. Methods Based on genomic statistics of seven different cystatins and three subtypes of lung cancer, we conducted a two‐sample Mendelian randomization (MR) study. The inverse‐variance weighted (IVW) method was the main approach for causality estimation. The weighted median, simple mode, weighted mode, and MR‐Egger regression methods were further employed to validate the main findings. In the sensitivity analysis, horizontal pleiotropy was assessed by MR‐Egger regression and Cochran’s Q test. MR‐PRESSO and Radial MR methods were used to identify heterogeneity and remove outliers. Results Genetically predicted Cystatin 8 was causally associated with squamous cell lung carcinoma (OR = 1.062, 95% CI: 1.004–1.124, p = 0.035). No causal relationships were found for genetically predicted cystatin 8, ‐B, ‐D, ‐F, or ‐M with squamous cell lung carcinoma, lung adenocarcinoma, and NSCLC. However, outliers were identified between Cystatin D, ‐M, and ‐F using MR‐PRESSO and Radial MR. After the removal of outliers, the association between Cystatin D and lung adenocarcinoma turned significant (OR = 1.178, 95% CI: 1.023–1.358, p = 0.023). Sensitivity analyses confirmed the robustness of main results after outliers removal. Conclusion Genetically predicted Cystatin 8 was causally associated with squamous cell lung carcinoma. Future population‐based studies are required to substantiate these results. |
| format | Article |
| id | doaj-art-e12d6c1a1dd5461382abdf642ba1c0e9 |
| institution | DOAJ |
| issn | 1752-6981 1752-699X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
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| series | The Clinical Respiratory Journal |
| spelling | doaj-art-e12d6c1a1dd5461382abdf642ba1c0e92025-08-20T03:08:33ZengWileyThe Clinical Respiratory Journal1752-69811752-699X2025-07-01197n/an/a10.1111/crj.70112Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization StudyChunling Zhang0Riya Wu1Hang Liu2Shihuan Yu3Department of Pulmonary Disease The First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang ChinaDepartment of Pulmonary Disease The First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang ChinaDepartment of Pulmonary Disease The First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang ChinaDepartment of Pulmonary Disease The First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang ChinaABSTRACT Introduction The cystatin family is particularly relevant in lung cancer research due to its links to inflammation, protease balance, and tumor progression. Although population‐based studies have documented associations between cystatin and lung cancer, causal relationships remain undetermined. Methods Based on genomic statistics of seven different cystatins and three subtypes of lung cancer, we conducted a two‐sample Mendelian randomization (MR) study. The inverse‐variance weighted (IVW) method was the main approach for causality estimation. The weighted median, simple mode, weighted mode, and MR‐Egger regression methods were further employed to validate the main findings. In the sensitivity analysis, horizontal pleiotropy was assessed by MR‐Egger regression and Cochran’s Q test. MR‐PRESSO and Radial MR methods were used to identify heterogeneity and remove outliers. Results Genetically predicted Cystatin 8 was causally associated with squamous cell lung carcinoma (OR = 1.062, 95% CI: 1.004–1.124, p = 0.035). No causal relationships were found for genetically predicted cystatin 8, ‐B, ‐D, ‐F, or ‐M with squamous cell lung carcinoma, lung adenocarcinoma, and NSCLC. However, outliers were identified between Cystatin D, ‐M, and ‐F using MR‐PRESSO and Radial MR. After the removal of outliers, the association between Cystatin D and lung adenocarcinoma turned significant (OR = 1.178, 95% CI: 1.023–1.358, p = 0.023). Sensitivity analyses confirmed the robustness of main results after outliers removal. Conclusion Genetically predicted Cystatin 8 was causally associated with squamous cell lung carcinoma. Future population‐based studies are required to substantiate these results.https://doi.org/10.1111/crj.70112causal correlationcystatinlung adenocarcinomaMendelian randomizationnon‐small cell lung cancersquamous cell lung carcinoma |
| spellingShingle | Chunling Zhang Riya Wu Hang Liu Shihuan Yu Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study The Clinical Respiratory Journal causal correlation cystatin lung adenocarcinoma Mendelian randomization non‐small cell lung cancer squamous cell lung carcinoma |
| title | Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study |
| title_full | Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study |
| title_fullStr | Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study |
| title_full_unstemmed | Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study |
| title_short | Causal Associations Between Cystatin and Lung Cancer: A Two‐Sample Mendelian Randomization Study |
| title_sort | causal associations between cystatin and lung cancer a two sample mendelian randomization study |
| topic | causal correlation cystatin lung adenocarcinoma Mendelian randomization non‐small cell lung cancer squamous cell lung carcinoma |
| url | https://doi.org/10.1111/crj.70112 |
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